Current development and future prospects in chemotherapy of tuberculosis
Open Access
- 21 June 2010
- journal article
- review article
- Published by Wiley in Respirology
- Vol. 15 (5) , 764-778
Abstract
Although treatment of drug‐susceptible tuberculosis (TB) under ideal conditions may be successful in ≥95% of cases, cure rates in the field are often significantly lower due to the logistical challenges of administering and properly supervising the intake of combination chemotherapy for 6–9 months. Success rates are far worse for multidrug‐resistant and extensively drug‐resistant TB cases. There is general agreement that new anti‐TB drugs are needed to shorten or otherwise simplify treatment for drug‐susceptible and multidrug‐resistant/extensively drug‐resistant‐TB, including TB associated with HIV infection. For the first time in over 40 years, a nascent pipeline of new anti‐TB drug candidates has been assembled. Eleven candidates from seven classes are currently being evaluated in clinical trials. They include novel chemical entities belonging to entirely new classes of antibacterials, agents approved for use against infections other than TB, and an agent already approved for limited use against TB. In this article, we review the current state of TB treatment and its limitations and provide updates on the status of new drugs in clinical trials. In the conclusion, we briefly highlight ongoing efforts to discover new compounds and recent advances in alternative drug delivery systems.Keywords
This publication has 142 references indexed in Scilit:
- Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy SubjectsAntimicrobial Agents and Chemotherapy, 2009
- Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trialThe Lancet, 2009
- Meropenem-Clavulanate Is Effective Against Extensively Drug-Resistant Mycobacterium tuberculosisScience, 2009
- PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO ReleaseScience, 2008
- Repeated Administration of High-Dose Intermittent Rifapentine Reduces Rifapentine and Moxifloxacin Plasma ConcentrationsAntimicrobial Agents and Chemotherapy, 2008
- Impact of the Interaction of R207910 with Rifampin on the Treatment of Tuberculosis Studied in the Mouse ModelAntimicrobial Agents and Chemotherapy, 2008
- The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosisProceedings of the National Academy of Sciences, 2008
- Powerful Bactericidal and Sterilizing Activity of a Regimen Containing PA-824, Moxifloxacin, and Pyrazinamide in a Murine Model of TuberculosisAntimicrobial Agents and Chemotherapy, 2008
- Irreversible Inhibition of the Mycobacterium tuberculosis β-Lactamase by ClavulanateBiochemistry, 2007
- Combination Chemotherapy with the Nitroimidazopyran PA-824 and First-Line Drugs in a Murine Model of TuberculosisAntimicrobial Agents and Chemotherapy, 2006